The avermectins are a series of eight macrocyclic lactones (“macrolides”) having a broad spectrum antiparasitic activity. These compounds, also designated as the “C-076 complex”, are produced by the soil microorganism Streptomyces avermitilis. The isolation and chemical structure of the eight individual components of the C-076 complex is disclosed e.g. in GB 1573955, which is herein incorporated by reference. Selective hydrogenation products of the C-076 compounds and derivatives thereof are disclosed in U.S. Pat. No. 4,199,569.
The milbemycins are a group of antiparasite macrolides structurally related to the C-076 complex, distinguished from the avermectins in that they lack the sugar residue attached at the C-13 position. Examples of such compounds are disclosed e.g. in GB 1390336, EP 170006, EP 254583, EP 334484 and EP 410615.
Ivermectin falls within the group of avermectins. This substance consists of a mixture of 80% or more of avermectin B1a and 20% or less of avermectin B1b. The structural formula of avermectin B1a and avermectin B1b, is illustrated below:

Avermectin B1a: R═C2H5; Avermectin B1b: R═CH3.
Ivermectin is a semi synthetic, anti-helmintic agent suitable for oral administration. In the mid 1980's, this active ingredient was introduced on the market as probably the broadest-spectrum anti-parasite medication ever. Traditionally it was used against worms (except tapeworms), but more recently it has been found to be effective against most mites and some lice as well. It is sold under the trademark names Stromectol in the United States, Mectizan in Canada by Merck, and Ivexterm in Mexico by Valeant Pharmaceuticals International. Mectizan is currently used to help eliminate river blindness (onchocerciasis) and stop transmission of lymphatic filariasis. Ivermectin kills the parasite by interfering with the nervous system and muscle function, in particular by enhancing inhibitory neurotransmission. The drug binds and activates glutamate-gated chloride channels (GluCls) present in neurons and myocytes. The main concern in connection with the administration of ivermectin is its neurotoxicity, which in most mammalian species can give rise to CNS depression and ataxia, as might be expected from potentiating inhibitory GABA-ergic synapses. Ivermectin is mainly used in humans in the treatment of onchocerciasis, but it is also effective against other worm infestations, such as strongyloidiasis, ascariasis, trichuriasis and enterobiasis. More recent evidence supports its off-label use in the treatment of mites such as scabies, usually limited to cases that prove resistant to topical treatments and/or which are in an advanced state, such as Norwegian scabies.
The present inventors have now surprisingly found that ivermectin is capable of inhibiting the enzymatic activity of Flavivirus helicase, an enzyme required for the replication of Flaviviruses.